Burkholderia (Pseuudomonas) cepacia is intrinsically highly resistant to most of the available antibiotics. Our previous data from analysis by MIC determination and SDS-PSAGE of independently induced highly resistant mutants (to ciprofloxacin (cip) and to trimethoprim-sulfamethoxazole (T/S)) of B.cepacia suggest that this resistance is mediated by some changes in outer membrane proteins and major changes in the LPS profile. Negative ion FAB analysis of the whole LPS showed over sixty distinct peaks ranging in mass from 120 to 1544 daltons. These peaks are groups in several clusters representing different carbohydrate composition. A difference in mass of 28 within each cluster corresponds to a natural difference in -C2 units in the fatty acid chains on lipid A. Changes in peak abundances and in mass in the spectra of LPS from antibiotic-resistant mutants (both T/S and cip) reflect differences in LPS composition, such as in fatty-acid side chains and carbohydrate content.